dinaciclib and Polycystic-Kidney--Autosomal-Dominant

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent monogenic human disease, but to date, only one therapy (tolvaptan) is approved to treat kidney cysts in ADPKD patients. Cyclin-dependent kinase 5 (CDK5), an atypical member of the cyclin-dependent kinase family, has been implicated as a target for treating ADPKD. However, no compounds have been disclosed to date that selectively inhibit CDK5 while sparing the broader CDK family members. Herein, we report the discovery of CDK5 inhibitors, including

Topics: Cell Proliferation; Cyclin-Dependent Kinase 5; Cyclin-Dependent Kinases; Drug Design; Drug Discovery; HEK293 Cells; Humans; Models, Molecular; Polycystic Kidney, Autosomal Dominant; Protein Kinase Inhibitors; Structure-Activity Relationship; Substrate Specificity